These mutants/Par-4 may be effective against all cancers. Cancer causes the death of hundreds of thousands of people each year. Treatments for cancer are not always effective.
Cancer is difficult to treat because the development of cancer is a multistep process involving accumulation of multiple genetic aberrations. Most notable among such alterations is the loss of apoptotic responses that normally serve as built in checkpoints against the emergence of cell populations with dysfunctional traits or the acquisition of prosurvival mechanisms that override the apoptotic signals. The loss of apoptotic mechanisms often results in abridged response to cancer therapy. Therefore, alternate or combinatorial approaches to kill the cancer cells and induce tumor regression are often actively pursued by researchers and physicians.
Especially difficult to treat are those cancers which are hormonally related. These cancers include prostate cancer and breast cancer.
Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer-related deaths in men in the United States. According to the American Cancer Society, about 198,100 new cases of prostate cancer will be diagnosed in the United States in 2001, and about 31,500 men will die of the disease. See www.cancer.org/docroot/STT/SH—0—2001.
Prostate cancer cells fall into two types: androgen dependent and androgen independent. Current treatment for prostate cancer involves hormone treatments that remove testosterone, thereby killing the prostate cancer cells that are dependent on the hormone. However, androgen independent cancer cells, which are the cells responsible for prostate cancer spreading to other areas, are not killed by this treatment. About 30 percent of patients develop androgen independent prostate cancer within three years of initial treatment, and patients with androgen independent cancer have a poor prognosis in both localized and disseminated disease. Currently, there is a 34% chance of recurrence of prostate cancer. The median time to development of clinical metastasis after biochemical recurrence is 8 years. Once treatment resistant metastatic disease is developed, the median time to death is an additional 5 years. Pound et al., JAMA (1999) 271: 1591-97.
Another common cancer linked to hormone action is breast cancer. Current treatments for breast cancer include surgery to remove the cancer, radiation therapy, chemotherapy, peripheral stem cell transplantation, bone marrow transplantation, hormonal therapy, and biological immunotherapy (using the immune system to fight cancer).
Side effects of cancer therapies are often severe. They include nausea, vomiting, pain, poor appetite, wasting, cachexia, diarrhea, burning in the stomach, stress, planter warts, nerve death-neuropathy, radiation burns, fatigue, constipation, anemia, anxiety, weakened immune system, dry skin, bone marrow suppression and hair loss.
An essential feature of anticancer strategies is the selective action against cancer cells, with little or no damage inflicted in normal cells. Identification of molecules that can specifically target tumor cells, therefore, appropriately constitutes a significant area of cancer research. Such molecules with selective action against tumor cells are valuable not only for their therapeutic potential; but also for their potential applications as tools for dissection of fundamental differences between normal and cancer cells. Thus, the identification of a molecule that can specifically target certain types of hormonally linked cancers would be extremely useful.